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Locating potential enhancer elements by comparative genomics using the EEL software

Abstract

This protocol describes the use of Enhancer Element Locator (EEL), a computer program that was designed to locate distal enhancer elements in long mammalian sequences. EEL will predict the location and structure of conserved enhancers after being provided with two orthologous DNA sequences and binding specificity matrices for the transcription factors (TFs) that are expected to contribute to the function of the enhancers to be identified. The freely available EEL software can analyze two 1-Mb sequences with 100 TF motifs in about 15 min on a modern Windows, Linux or Mac computer. The output provides several hypotheses about enhancer location and structure for further evaluation by an expert on enhancer function.

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Figure 1: The scoring function of EEL.
Figure 2: A file containing the position-specific binding profile for the TF Hunchback obtained from the JASPAR database.
Figure 3: The main window of EEL when the program is started.
Figure 4: Display shown during addition of new sequences to the analysis.
Figure 5: Display shown during addition of new binding motif matrices to the analysis.
Figure 6: The window for parameters of the TFBS search.
Figure 7: A window for parameters of the local alignment procedure for enhancer prediction.
Figure 8: The window showing the predicted enhancer elements.
Figure 9: The score distributions of genome-wide EEL alignments for human and mouse.

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Acknowledgements

This work was supported by the 'Translational Genome-Scale Biology' and the 'From Data to Knowledge' Centers of Excellence of the Academy of Finland and by the 'BioSapiens' and the 'Regulatory Genomics' projects of the European Union.

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Correspondence to Kimmo Palin.

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Palin, K., Taipale, J. & Ukkonen, E. Locating potential enhancer elements by comparative genomics using the EEL software. Nat Protoc 1, 368–374 (2006). https://doi.org/10.1038/nprot.2006.56

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